The serotonin agonist N(a,a,u-trifluoro-m-tolyl)piperazine (TFMPP) is a potent ligand for the serotonin system (R. Paoletti et al., Serotonin: From cell Biology 10 Pharmacology and Therapeutics, 39-51. 1990 by Kluwer Academic Publisher; R. A. Glennon Newrosience & Biobeh Rev.. 1990. 14. 35.). Angelini and co-workers previously synthesized the C.a (F-l8]TFMPP but the low specific activity (less than 0.2GBq/mmol) limited the application of this ligand (J. Lab. Comp. & Rodiopharm. 1990. 28. 1441.). We have recently reported the formation of phenylpiperazines by a novel alumina supported bis-alkylation. We report here the application of this method and biological evaluation of 3-(F-l8]FTFMPP, a fluoro derivative of TFMPP. Reaction of (F-l8] fluoride with 3,5-dinitrobenzotrifluoride gave the 3-(F-l8]fluoro-5-nitrobenzotrifluoride in 70% yield. Reduction of the nitro group with Raney nickel and hydrazine hydrate gave the (F-18]aniline derivative in 70% yield. Finally, the phenylpiperazine was constructed by reaction of the (F-l8]aniline derivative with bis(2-bromoethyl-N-(ethoxy carbonyl)amine on basic alumina (pH=9) as a solid support. After extraction of the activity with basic MeOH and HPLC purification on normal phase the final product- [F-18]FTFMPP was obtained in 50% yield (98% radiochemical purity). The specific activity of the final product was l00GBq/mmol. The binding affinity of FTFMPP to 5-HT receptor was determined (Ki=28-100 nM) and found to be similar to the binding affinity of the TFMPPP(l6O- 180 nM). The biodistribution of [F-18]FTFMPP was performed in rats. The results showed that the compound accumulates in lung, brain and liver-8.1+/-1.4, 2.11+/-0.29 and 4.9+/-0.12 %ID/g respectively, 30 min post injection. Low tracer uptake by bone indicated no in vivo defluorination of the tracer. The brain/blood and brain/muscle ratios 30 mill post injection were l0 and 8.5 respectively. A blocking experiment at 30 min post injection with the selective high affinity 5HT1A agonist 8-H-DPAT (5mg/kg, co-administated with the radiotracer) showed that the uptake in the cortex. cerebellum and hippocampus was inhibited by 42%, 30%, and 26% respectively. Quipazine which has low affinity for the 5-HT1 receptor and moderate affinity for 5-HT2/3 receptor did not block the binding of [F-l8] FTFMPP at 30 and 60 min. In conclusion, we have prepared a fluorinated derivative of TFMPP, demonstrated that it has similar binding affinity to the parent compound and evaluated its biodistribution in.vivo. The new reaction to produce the piperazine ring show applicability to the synthesis of other radiopharmaceuticals.